Fundamental characterization of host-guest chemistry in the gas phase and its applications in carbohydrate analysis

다국어 초록 (Multilingual Abstract)

Mass spectrometry (MS) is an analytical technique with advantages such as low sample consumption, high sensitivity, and compatibility with chromatographic techniques. Hence, MS is nowadays widely utilized in various fields of science such as proteomics, environmental science, and pharmaceutical science. Recently, MS also contributed to the advancement of glycomics. Investigation of carbohydrates using MS and tandem mass spectrometry (MSn) facilitates their structure determination and precise quantification. Nevertheless, the carbohydrate analysis by MS generally requires several sample preparation steps such as pre-derivatization, which can lead to incorrect determination of carbohydrates, because of their high structural complexities. In this thesis, a combination of host-guest chemistry and MS was utilized to develop new methods for the efficient analysis of diverse carbohydrates. Host–guest interactions of carbohydrates with a host receptor in the gas phase allowed us to distinguish subtle structural differences among carbohydrates by MS, and achieve high–accuracy quantification.
In Chapter 1, a background on carbohydrate analysis using MS and host–guest chemistry of hydrophilic guests is introduced. Previous studies on the host–guest chemistry in the gas phase are also reviewed.
In Chapter 2, distinct host–guest interactions of neutral hexose isomers with a host receptor, cucurbit[7]uril (CB[7]), in the gas phase are studied using two MS techniques, collision-induced dissociation (CID) and ion mobility spectrometry (IMS), and other analytical techniques. It is observed that host–guest interactions
generate different fragmentation patterns upon collisional activation, facilitating effective identification and quantification of the isomers. In addition, these unique host–guest phenomena occur because of distinct host–guest interactions between CB[7] and neutral hexose isomers in the gas phase.
In Chapter 3, the gas-phase host–guest chemistry of 12 monosaccharide derivatives including hexosamines, N-acetylhexosamines, deoxyhexoses, and uronic acids was investigated by using MSn and IM-MS. The results of the study served as the basis to extend the applicability of gas-phase host–guest chemistry and establish
a comprehensive system for qualifying and quantifying diverse types of constituent monosaccharide isomers in a simple manner.
In Chapter 4, the developed system was further extended to a practical application of the gas-phase host–guest chemistry. This study revealed that the host–guest system can be effectively utilized for accurate quantification of N-glycolylneuraminic acid and N-acetylneuraminic acid in therapeutic glycoproteins, which were difficult to analyze without additional sample preparation steps.

목차 (Table of Contents)

• I. General Introduction 1
• 1.1. Introduction 2
• 1.2. Reference 6
• II. Characterization and Applications of Distinct Gas-phase Binding of Cucurbit[7]uril to Different Neutral Hexose Isomers 10
• 2.1. Introduction 11
• 2.2. Results and Discussion 13
• 2.3. Conclusion 19
• 2.4. Materials and Methods 20
• 2.5. References 25
• 2.6. Figures and Tables 30
• III. Expanded Applications of the Distinct Gas-phase Binding of Cucurbit[7]uril for Analyzing Diverse Types of Monosaccharide Derivative Isomers 48
• 3.1. Introduction 49
• 3.2. Results and Discussion 52
• 3.3. Conclusion 58
• 3.4. Materials and Methods 59
• 3.5. References 62
• 3.6. Figures and Tables 67
• IV. A Practical Application of Gas-phase Hostguest Chemistry of Cucurbit[7]uril to Sialic Acids in Therapeutic Glycoproteins 89
• 4.1. Introduction 90
• 4.2. Results and Discussion 93
• 4.3. Conclusion 100
• 4.4. Materials and Methods 101
• 4.5. References 107
• 4.6. Figures and Tables 113
• V. Summary in Korean 133
• VI. Acknowledgement 136
• VII. Curriculum Vitae 138